The isolation and characterization of 24,25-dihydroxycholecalciferol (24,25-dihydroxyvitamin D.sub.3 ) (M. F. Holick et al., Biochemistry, 11, 4251 [1972]), and the subsequent finding that this second most abundant metabolite of vitamin D.sub.3 (J. L. Omdahl and H. F. DeLuca, Physiological Reviews, 53, 327 [1973]) preferentially stimulates intestinal calcium transport without, at comparable dose levels, mobilizing bone calcium, prompted extensive investigation of the physiological role played by this metabolite (see, for example, H. K. Schnoes and H. F. DeLuca, Vitamins and Hormones, 32, 395 [1974]). These investigations have been hampered by the minute amounts of the metabolite available from natural sources, the lack of information concerning the stereochemistry of the metabolic hydroxyl group at C-24 and the effect of the configuration of this group on the biological activity exhibited by 24,25-dihydroxycholecalciferol.
In 1973, M. Seki et al., Chem. Pharm. Bull. (Japan), 21, 2783(1973) described the conversion of desmosterol acetate to 24.xi. , 25-dihydroxycholesterol, a precursor of 24,25-dihydroxycholecalciferol. Shortly thereafter, H. -Y. Lam et al., Biochemistry, 12, 4851 (1973) and J. Redel et al., Compt. rend. Acad. Soc. (Paris), 278, 529 (1974) disclosed syntheses of 24.xi. ,25 -dihydroxycholecalciferol starting from 3.beta. -acetoxy-27-nor-5-cholesten-25-one and desmosterol acetate, respectively. These syntheses are non-stereospecific yielding mixtures of stereoisomers at C-24. M. Seki et al., Tetrahedron Letters, 15 (1975) recently described the separation of 24.xi. ,25-dihydroxycholesterol into the 24R- and 24S-isomers and the conversion of the 24R- and 24S-isomer into 24R,25- and 24S,25-dihydroxycholecalciferol, respectively. This synthesis suffers from the inherent disadvantages associated with the separation step. Thus, stereospecific syntheses of 24R, 25- and 24S, 25-dihydroxycholecalciferol utilizing 24,25-dihydroxycholesterol derivatives of known stereochemistry at C-24 overcoming the deficiencies of the prior art processes and making this important metabolite of vitamin D.sub.3 readily available for biological, clinical and therapeutic use would represent an important contribution to the advancement of the state of the art in the vitamin D field.